Spatial Profiling of CXCL10 in Breast Cancer: TAMs' Mediation of Immune Response

Abstract

Abstract Background Tumor-Associated Macrophages play a significant role in the tumor microenvironment of breast cancer, influencing its growth and progression. Their presence is associated with key processes such as angiogenesis and immunomodulation, impacting the immune system response and tumor aggressiveness. Methods This study employed various methods to analyze scRNA-seq and spatial transcriptome data. The scRNA-seq data underwent thorough processing and analysis, with a specific focus on breast cancer subtypes. The CellChat R package was employed to analyze and visualize cell-cell communication networks within the scRNA-seq data. hdWGCNA, conducted in R, involved multiple steps such as data preprocessing, gene network construction, module identification, module preservation analysis, and functional enrichment analysis. To analyze the pseudotime dynamics of endothelial cells, Monocle3 was utilized. The spatial data for normal skin and leprosy were obtained and analyzed using the SPATA2 and semla R packages, facilitating the integration of spatial and single-cell data. Results The study utilized scRNA-seq and spatial transcriptome data to comprehensively analyze 40 samples of breast cancer, including ER+, HER2+, and TNBC subtypes, alongside normal mammary tissue. Distinct cellular clusters were identified, and myeloid cells were characterized into four subtypes. Comparative analyses across breast cancer subtypes highlighted variations in the expression of the CXCL10 gene, and hdWGCNA provided insights into molecular landscapes. Trajectory inference analysis revealed pseudotime dynamics in myeloid cells, with specific gene expression changes. Spatial transcriptome profiling in TNBC and HER2 + breast cancer showed unique cellular clusters and gene expression patterns within the tumor microenvironment. The integration of spatial and single-cell data emphasized the distribution of cell types and spatial enrichment of gene expression signatures. Conclusions TAMs emerge as key players engaging in multifaceted interactions with neighboring cell types within the intricate context of breast cancer. These identified genes, particularly CXCL10, assume central roles in regulating various facets of myeloid cell physiology and modulating immune responses. The observed increase in CXCL10 expression in TNBC macrophages suggests a potential association with T lymphocyte activity and myeloid cell chemotaxis, implicating its significance in the intricate immune response dynamics within the TNBC microenvironment.